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SuEllen J. Pommier PhD, Ariel Hernandez BS, Esther Han MD, Kristen Massimino MD, Patrick Muller BS, Brian Diggs PhD, Erin Chamberlain BS, Jennifer Murphy MD, Juliana Hansen MD, Arpana Naik MD, John Vetto MD, Rodney F. Pommier MD
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The process by which breast cancer stem cells arise is unknown. It may be that the benign stem cells in breast tissue are transformed into malignant stem cells through the acquisition of genetic abnormalities. In this study, we collected and compared benign and malignant breast stem/progenitor cells to determine whether specific genetic abnormalities occur in breast cancer stem/progenitor cells within the human body.
Fresh surgical specimens from benign and malignant breast tissues were obtained directly from the operating room and examined. Cells variably expressing stem cell-associated surface markers CD49f and CD24 were collected by fluorescence-activated cell sorting. The frequencies of these cells in benign and malignant breast tissues were ascertained. Oncogenetic mutation analyses were performed and expression of stem cell-associated genes was measured.
The frequencies of stem/progenitor cells were similar between benign and malignant tissues. Stem cell-associated gene expression also was similar between benign and malignant stem cells. Genetic mutations in the PIK/AKT pathway were found in 73% of the tumors’ stem cells, specifically within two subpopulations. No mutations were found in stem/progenitor cell subpopulations from benign breast tissue.
The results of this study suggest that, following malignant transformation, breast cancer stem/progenitor cells retain their stem cell functions and relative frequencies. In addition, they develop malignant capabilities by acquiring mutations in genes critical for maintaining normal cellular metabolism and proliferation.
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